Figure 1.

(A–C) Cryo-EM images are usually acquired on heterogeneous samples. Contaminants (light blue), denatured or partially disassemble complexes (light red) as well as different protein complex conformations (gold) are imaged together with the specimen (gray). (D) General approach workflow to handle sample heterogeneity during image processing. Processes (black boxes), iterative process (green boxes), and specific input data (blue boxes) are indicated. The consensus reconstruction is obtained from an initially heterogeneous dataset and it will be used as the initial reference for more specific refinement protocols to deal with sample heterogeneity.